Combined varenicline and naltrexone treatment reduces smoking topography intensity in heavy-drinking smokers

Abstract

Heavy drinking smokers constitute a distinct sub-population of smokers for whom traditional smoking cessation therapies may not be effective. Recent evidence suggested that combined varenicline (VAR) and naltrexone (NTX) therapy may be more efficacious than either monotherapy alone in reducing smoking and drinking-related behavior in this population. The manner in which individuals smoke a cigarette (i.e., smoking topography) may be predictive of smoking cessation outcomes, yet the effects of smoking pharmacotherapies on puffing behavior have not been thoroughly examined. Therefore, the current double-blind medication study examined the effects of VAR alone (1mg BID), low dose NTX alone (25mg QD), the combination of VAR+NTX, and placebo on smoking topography measures in heavy drinking, non-treatment seeking daily smokers (n=120). After a 9-day titration period, participants completed a laboratory session in which they smoked their first cigarette of the day using a smoking topography device following 12h of nicotine abstinence and consumption of an alcoholic beverage (BrAC=0.06g/dl). The primary measures were puff count, volume, duration, and velocity and inter-puff interval (IPI). Independent of medication group, puff velocity and IPI increased, while puff volume and duration decreased, over the course of the cigarette. The active medication groups, vs. the placebo group, had significantly blunted puff duration and velocity slopes over the course of the cigarette, and this effect was particularly evident in the VAR+NTX group. Additionally, the VAR+NTX group demonstrated lower average IPI than the monotherapy groups and lower average puff volume than all other groups. These results suggest that smoking pharmacotherapies, particularly the combination of VAR+NTX, alter smoking topography in heavy drinking smokers, producing a pattern of less intense puffing behavior. As smoking topography has been predictive of the ability to quit smoking, future studies should examine how smoking pharmacotherapies' effects on puffing behavior relate to smoking cessation outcomes.

Keywords: Heavy drinking smokers; Naltrexone; Smoking topography; Varenicline.

Figure 1

Puff duration (A), velocity (B), volume (C), and IPI (D) as predicted by medication group and proportion of the cigarette smoked. Brackets with an asterisk refer to a significant post hoc difference (p < 0.05) between an active medication group and the placebo group. Raw data is presented for puff velocity and volume, while log transformed data is presented for duration and IPI. A) Puff Duration. Active medication groups together had blunted slopes as compared with the placebo group (Cig% × Active Contrast, p < 0.05). Post hoc comparisons indicated that only the combined VAR+NTX group had a significantly flatter slope than the placebo group (p < 0.05). B) Puff velocity. Active medication groups together had blunted slopes compared with the placebo group (Cig% × Active Contrast, p < 0.05). Post hoc analyses indicated that only the combined VAR + NTX group had a significantly flatter slope than placebo (p < 0.05). C) Puff volume. The combined VAR+NTX group had marginally lower average volume than monotherapy groups (Combined Contrast main effect, p = 0.08). Post hoc comparisons indicated that only the combined VAR+NTX group had significantly lower average puff volume as compared with placebo (p < 0.05). D) IPI. The combined VAR+NTX group was found to have lower average IPI than the monotherapy groups (Combined contrast main effect, p < 0.05). However, post hoc comparisons did not reveal differences between the individual active medication groups and the placebo group.